Membrane affinity of antituberculotic drug conjugate using lipid monolayer containing mycolic acid

Cs B. Pénzes, D. Schnöller, K. Horváti, Sz. Bősze, G. Mező, E. Kiss

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Surface behaviour of mixed monolayers of DPPC and mycolic acid as a specific membrane component of Mycobacterium tuberculosis were studied by Langmuir-balance technique. Additivity analysis of the surface pressure-area isotherms showed that mixed layers are expanded at higher temperature (36 °C) while negative excess surface areas were obtained depending on the composition at lower temperature (24 °C). Strong condensation and aggregated structure of the mixed layer was revealed by AFM. Isoniazid (INH) which is an effective bactericidal synthetic therapeutic agent for the treatment of tuberculosis was conjugated with a tuftsin derivative (TKPKG) and a lipophilic molecule (palmitic acid) to enhance its specific delivery and cellular uptake. Membrane affinity of the lipopeptide conjugate pal-T 5-(INH) 2 was estimated from penetration experiments using model lipid monolayers. Degree of penetration was higher into mycolic acid containing monolayers than to phospholipon. The lipopeptide conjugate pal-T 5-(INH) 2 presented the highest membrane affinity to DPPC:MA layer at lower temperature. Temperature dependent organization of the mixed film was in accordance with the degree of penetration indicating the importance of structural characteristics in molecular interaction between drug and membrane components.

Original languageEnglish
Pages (from-to)142-148
Number of pages7
JournalColloids and Surfaces A: Physicochemical and Engineering Aspects
Volume413
DOIs
Publication statusPublished - Nov 5 2012

Fingerprint

Mycolic Acids
Lipids
affinity
lipids
Monolayers
drugs
membranes
Lipopeptides
Membranes
tuberculosis
acids
penetration
Acids
Pharmaceutical Preparations
Tuftsin
palmitic acid
Palmitic acid
Temperature
Molecular interactions
Palmitic Acid

Keywords

  • DPPC
  • Langmuir monolayer
  • Lipopeptide drug conjugate
  • Membrane affinity
  • Mycolic acid

ASJC Scopus subject areas

  • Colloid and Surface Chemistry

Cite this

Membrane affinity of antituberculotic drug conjugate using lipid monolayer containing mycolic acid. / Pénzes, Cs B.; Schnöller, D.; Horváti, K.; Bősze, Sz.; Mező, G.; Kiss, E.

In: Colloids and Surfaces A: Physicochemical and Engineering Aspects, Vol. 413, 05.11.2012, p. 142-148.

Research output: Contribution to journalArticle

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